Clinical Practice Research Datalink Research Articles

The implications of competing risks and direct treatment disutility in cardiovascular disease and osteoporotic fracture: risk prediction and cost effectiveness analysis.

Clinical guidelines commonly recommend preventative treatments for people above a risk threshold. Therefore, decision-makers must have faith in risk prediction tools and model-based cost-effectiveness analyses for people at different levels of risk. Two problems that arise are inadequate handling of competing risks of death and failing to account for direct treatment disutility (i.e. the hassle of taking treatments). We explored these issues using two case studies: primary prevention of cardiovascular disease using statins and osteoporotic fracture using bisphosphonates. Externally validate three risk prediction tools [QRISK®3, QRISK®-Lifetime, QFracture-2012 (ClinRisk Ltd, Leeds, UK)]; derive and internally validate new risk prediction tools for cardiovascular disease [competing mortality risk model with Charlson Comorbidity Index (CRISK-CCI)] and fracture (CFracture), accounting for competing-cause death; quantify direct treatment disutility for statins and bisphosphonates; and examine the effect of competing risks and direct treatment disutility on the cost-effectiveness of preventative treatments. Discrimination and calibration of risk prediction models (Clinical Practice Research Datalink participants: aged 25-84 years for cardiovascular disease and aged 30-99 years for fractures); direct treatment disutility was elicited in online stated-preference surveys (people with/people without experience of statins/bisphosphonates); costs and quality-adjusted life-years were determined from decision-analytic modelling (updated models used in National Institute for Health and Care Excellence decision-making). CRISK-CCI has excellent discrimination, similar to that of QRISK3 (Harrell's c = 0.864 vs. 0.865, respectively, for women; and 0.819 vs. 0.834, respectively, for men). CRISK-CCI has systematically better calibration, although both models overpredict in high-risk subgroups. People recommended for treatment (10-year risk of ≥ 10%) are younger when using QRISK-Lifetime than when using QRISK3, and have fewer observed events in a 10-year follow-up (4.0% vs. 11.9%, respectively, for women; and 4.3% vs. 10.8%, respectively, for men). QFracture-2012 underpredicts fractures, owing to under-ascertainment of events in its derivation. However, there is major overprediction among people aged 85-99 years and/or with multiple long-term conditions. CFracture is better calibrated, although it also overpredicts among older people. In a time trade-off exercise (n = 879), statins exhibited direct treatment disutility of 0.034; for bisphosphonates, it was greater, at 0.067. Inconvenience also influenced preferences in best-worst scaling (n = 631). Updated cost-effectiveness analysis generates more quality-adjusted life-years among people with below-average cardiovascular risk and fewer among people with above-average risk. If people experience disutility when taking statins, the cardiovascular risk threshold at which benefits outweigh harms rises with age (≥ 8% 10-year risk at 40 years of age; ≥ 38% 10-year risk at 80 years of age). Assuming that everyone experiences population-average direct treatment disutility with oral bisphosphonates, treatment is net harmful at all levels of risk. Treating data as missing at random is a strong assumption in risk prediction model derivation. Disentangling the effect of statins from secular trends in cardiovascular disease in the previous two decades is challenging. Validating lifetime risk prediction is impossible without using very historical data. Respondents to our stated-preference survey may not be representative of the population. There is no consensus on which direct treatment disutilities should be used for cost-effectiveness analyses. Not all the inputs to the cost-effectiveness models could be updated. Ignoring competing mortality in risk prediction overestimates the risk of cardiovascular events and fracture, especially among older people and those with multimorbidity. Adjustment for competing risk does not meaningfully alter cost-effectiveness of these preventative interventions, but direct treatment disutility is measurable and has the potential to alter the balance of benefits and harms. We argue that this is best addressed in individual-level shared decision-making. This study is registered as PROSPERO CRD42021249959. This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 15/12/22) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 4. See the NIHR Funding and Awards website for further award information.

Prescribing trends of proton pump inhibitors and histamine blockers among children in the United Kingdom (1998-2019): A population-based assessment.

To describe the prescribing trends of proton pump inhibitors (PPIs) and H2 receptor antagonists (H2 RAs) among children with gastroesophageal reflux in the United Kingdom between 1998 and 2019. We conducted a population-based retrospective cohort study using data from the Clinical Practice Research Datalink that included all children aged ≤18 years with a first ever diagnosis of gastroesophageal reflux between 1998 and 2019. Using negative binomial regression, we estimated crude and adjusted annual prescription rates per 1000 person-years and corresponding 95% confidence intervals (CIs) for PPIs and H2 RAs. We also assessed rate ratios of PPIs and H2 RAs prescription rates to examine changes in prescribing over time. Our cohort included 177 477 children with a first ever diagnosis of gastroesophageal reflux during the study period. The median age was 13 years (IQR: 1, 17) among children prescribed PPIs and 0.2 years (IQR: 0.1, 0.6) among those prescribed H2 RAs. The total prescription rate of all GERD drugs was 1468 prescriptions per 1000 person-years (PYs) (95% CI 1463-1472). Overall, PPIs had a higher prescription rate (815 per 1000 PYs, 95% CI 812-818) than H2 RAs (653 per 1000 PYs 95% CI 650-655). Sex- and age-adjusted rate ratios of 2019 versus 1998 demonstrated a 10% increase and a 76% decrease in the prescription rates of PPIs and H2 RAs, respectively. Prescription rates for PPIs increased, especially during the first half of the study period, while prescription rates for H2 RA decreased over time.

Using an expanded algorithm to estimate prevalence of amyotrophic lateral sclerosis in U.S. and UK.

There is an increasing need to better understand the burden of amyotrophic lateral sclerosis (ALS) using real-world data (RWD). However, identifying ALS cases using RWD presents several challenges due to the rarity of ALS and the differences in database coding systems. MarketScan claims, and the UK Clinical Practice Research Datalink (CPRD) databases were searched for diagnosis codes of ALS or MND, the only drugs approved for treating ALS (riluzole and edaravone) and clinical visits with 12-month enrolment prior to 1 January 2011. The main algorithm required ≥ 1 ALS diagnosis code together with prescriptions or clinical visits. We expanded the existing algorithm to identify unspecific (possible) ALS group that had codes for motor neuron disease (MND) and the ALS drugs. The study period was from 1 January 2011 until 31 December 2020. We identified 16,246 patients with ≥ 1 ALS code in Marketscan (denominator n = 85,279,619), yet only 184 were found in the UK CPRD (denominator n = 21,318,589). Using the main algorithm 9,433 ALS patients were included in MarketScan, with a prevalence ranged between 4.5 per 100,000 in 2019 and 6.2 in 2015. In MarketScan, 3,658 (4.3 per 100,000) had ≥ 1 MND code and the ALS drug codes (possible cases). In CPRD, 47.9% of 2,785 patients with ≥ 1 MND code had a prescription for riluzole (6.3 per 100,000), regarded as possible ALS cases. The expanded algorithm enabled the identification of a large population with ALS, or possible ALS, and the estimation of ALS prevalence in MarketScan and CPRD.

P488 Development and validation of a risk prediction tool for inflammatory bowel disease (IBD) diagnosis in patients presenting in primary care with abdominal symptoms, a UK based study

Abstract Background There are no prediction models for a diagnosis of inflammatory bowel disease (IBD) in primary care. An IBD risk prediction tool has the potential to reduce the length of time patients have undiagnosed IBD symptoms and improve IBD clinical outcomes. Therefore, our aim was to develop and validate a risk prediction model for the diagnosis of IBD, ulcerative colitis (UC) and Crohn’s disease (CD) in men and women separately. Methods A population-based retrospective open cohort study using Clinical Practice Research Datalink (CPRD) Aurum database was undertaken between 1st January 2010 and 31st December 2019, including patients aged 18 years or older. Patients were followed from first presentation with lower gastrointestinal (GI) symptoms potentially related to IBD to the earliest of IBD diagnosis, loss to follow-up, death or study end. 2,054,530 patients were in the model derivation cohort and 673,320 patients in the validation cohort. Cox proportional hazards models were used to derive separate risk equations in men and women for IBD, UC and CD. Candidate predictors included demographic factors (age, sex, smoking, body mass index, Charlson comorbidity score, loperamide use), family history of IBD, co-existing conditions (anxiety, depression, irritable bowel syndrome (IBS), haemorrhoids), extraintestinal manifestations (EIM) (mouth ulcers, ophthalmic, primary sclerosing cholangitis, dermatological), investigations (hemoglobin, mean corpuscular volume, platelets, albumin, vitamin B12, ferritin, C-reactive protein, erythrocyte sedimentation rate, calprotectin level). Measures of calibration and discrimination (C-statistic and D-statistic, higher values indicate better discrimination) were determined in men and women separately in the validation cohort at 1,2,3 and 5 years after symptom presentation. Results In the derivation cohort, 15,105 (0.7%) patients had an IBD diagnosis (10.014 UC (66.3%) and 5,088 CD (33.7%)). The IBD prediction model included 41 and 40 predictors, and the UC model 37 and 36 predictors, in women and men respectively; the CD model included 37 predictors in both men and women. C-statistics and D-statistics in men were as follows: IBD model 0.77 and 1.74; UC model: 0.81 and 1.95; and CD model: 0.77 and 1.95, respectively. Similar values were observed in women.The measures of discrimination showed that the prediction models reliably differentiated patients with and without IBD, UC and CD in both sexes. Model calibration was good, tending to overestimate at higher risk thresholds in validation cohort. Conclusion A risk model of patient demographics, symptoms and investigations performs well for IBD, UC and CD and may help in prioritising suspected IBD referrals in symptomatic subjects in primary care.

P364 Faecal calprotectin testing in patients presenting with lower gastrointestinal symptoms; a retrospective primary care study in the United Kingdom

Abstract Background Faecal calprotectin (FC) is of value in differentiating Inflammatory Bowel Disease (IBD) from other causes of lower gastrointestinal (GI) symptoms and is recommended in national guidance. This study aims to examine the role of and factors associated with faecal calprotectin requesting in primary care. Methods Retrospective open cohort study using Clinical Practice Research Datalink (CPRD Aurum) of adults aged 18 years and above with lower GI symptoms between 2015 and 2019. FC requested 30 days before to 3 months after a lower GI symptom record in primary care were included. Logistic regression model was used to explore patient level factors associated with FC testing. Referral pathways and outcomes in terms of IBD diagnoses of patients with and without FC testing were also examined. Results Of 741,190 symptomatic patients, only 18,320 (2.5%) patients had a FC requested in primary care: median age 38.3 (IQR 28.9-50.7); 51.4% females. The percentage of FC requests in symptomatic patients increased from 0.02% in 2010 to 4.4% in 2019 (p=0.001). FC value of <50 ug/g and 50-200 ug/g were predominantly seen in patients with abdominal pain (42.1% and 37.9% respectively) while FC > 200 ug/g was predominantly seen in patients with diarrhoea (45.3%). The only patients with a significant risk of IBD with a FC 50-200ug/g were patients with rectal bleeding (8%). Factors associated with less FC requesting included: increasing age (>70 years aOR 0.16 ( 95% CI 0.15-0.18); female (0.89,0.86-0.92); Black (0.61, 0.56-0.66) or Asian (0.75, 0.70-0.80) ethnicity; obesity (0.89,0.85-0.93); lower socioeconomic status (0.91,0.86-0.98); comorbidity score >2 (0.73,0.68-0.79); and current smoking (0.89,0.85-0.92). Patients with change in bowel habit (7.31,6.90-7.75); rectal bleeding (2.04,1.95-2.13); diarrhoea (2.88,2.78-2.99) as a presenting symptom compared to abdominal pain and ex-smokers (1.06,1.03-1.11) had more FC requests. Of patients referred with a FC >200 ug/g, 21.5% were diagnosed with IBD but only 2.9% of patients with a FC 50-200ug/g. 27.8% patients with a normal FC test result were still referred to secondary care, of which only 0.4% had IBD. Conclusion Despite an increase in FC requests in recent years, only 4.4% of patients with relevant lower GI symptoms had an FC requested in primary care as recommended. Despite a negative FC test, 27.8% of patients were still referred to secondary care with very few patients diagnosed with IBD (0.4%).

Preventive treatment patterns in the adult migraine population: an observational UK study over 7 years

BackgroundCalcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are recommended by the United Kingdom National Institute of Health and Care Excellence for the prevention of migraine as treatment beyond third line. We report migraine prevalence and preventive treatment patterns in the adult United Kingdom primary care population over a 7.5-year period, focusing on patients ceasing ≥ 3 oral preventive medication classes.MethodsStudy populations were retrieved from the Clinical Practice Research Datalink GOLD database (study period: 19 September 2012 to 1 January 2020; inclusion criteria: ≥12 months follow-up, current-in-dataset, adult on 1 January 2020). Patients who used ≥ 1 oral preventive medication with ≥ 3-year follow-up after first prescription were considered preventive treatment users; class cessation was defined as cessation without evidence of restart within 6 months from end-of-supply date.ResultsOn 1 January 2020, 3.0% of the total study population were diagnosed with migraine (n = 81,190/2,664,306); of these, 42.4% were preventive treatment users (n = 34,448/81,190). The most frequently used oral migraine preventive medication classes were beta-blockers (n = 14,713), tricyclic antidepressants (n = 14,415) and antiepileptics (n = 6497). Among preventive treatment users, 7.7% (n = 2653/34,448) ceased ≥ 3 oral preventive medication classes; of these, 21.7% (n = 576/2653) had been referred to a neurologist.ConclusionsCompared to existing population-based estimates of migraine prevalence, our data further corroborates that a considerable proportion of patients with migraine do not seek treatment. Among those who sought primary care within a 7.5-year period, almost half received empirical oral preventive treatment. Importantly, nearly 1 of 10 preventive treatment users ceased ≥ 3 oral preventive medication classes, highlighting a need for additional therapeutic options. These patients may benefit from CGRP antagonists and/or injectable onabotulinumtoxinA; however, only a minority was referred to specialist care, where these options would be more available.Trial RegistrationNot applicable.

Risk of fibromyalgia following antibiotic prescriptions: Apopulation-based case-control study.

The health of the gut microbiome is now recognized to be an important component of the gut-brain axis which itself appears to be implicated in pain perception. Antibiotics are known to create dysbiosis in the microbiome, so whether fibromyalgia is more commonly diagnosed after antibiotic prescriptions provides a means of exploring the role of the microbiome in the experience of chronic pain. A case-control study was carried out using electronic health records collected in the UK's Clinical Practice Research Datalink (CPRD), a comprehensive database of primary care consultations. For each case of diagnosed fibromyalgia, three controls were identified and matched by age, gender and GP practice. The exposure variable was the number and timing of antibiotic prescriptions over previous years. The analysis involved adjusting for a wide range of co-variates that might be possible confounders. A total of 44,674 cases of fibromyalgia were identified together with 133,513 controls. After adjusting for co-variates, it was found that both the total number of prescriptions and their timing was associated with an FM diagnosis. For example, the quartile with the highest number of prescriptions and that with the longest exposure had a greater than three-fold increase in FM diagnoses (number of prescriptions: odds ratio 3.92; 95% CIs: 3.71-4.13; exposure odds ratio 3.28; CIs: 3.13-3.43). Some antibiotics (such as tetracyclines and metronidazole) seemed to confer greater risk than others. The results lend support for prior antibiotics being an important risk factor for a diagnosis of FM. This study shows an association between the volume as well as timing of prior antibiotic prescriptions and of a subsequent diagnosis of fibromyalgia in primary care.

Real-world evidence of epidemiology, patient characteristics, and mortality in people with drug-resistant epilepsy in the United Kingdom, 2011-2021.

A third of people with epilepsy are drug resistant. People with drug-resistant epilepsy (DRE) have a higher risk of mortality and physical injuries than those who respond to anti-seizure medication (ASM). This study describes patient characteristics, comorbidities, and mortality in people with DRE in the UK. The Clinical Practice Research Datalink was utilised to select people with DRE prescribed a third ASM between 1 January 2011 and 31 March 2021. Annual incidence and prevalence of DRE, patient characteristics, comorbidities, and mortality rates were analysed. Subgroup analysis was performed by age, sex, presence of intellectual disabilities and time from epilepsy diagnosis to DRE. A total of 34,647 people with DRE were included (mean ± SD age 42.68 ± 23.59years, 52.6% females). During the study period, annual DRE incidence ranged from 1.99% to 3.12%. As of 31 March 2021, DRE prevalence was 26.6% (95% confidence interval [CI] 26.3%-26.8%). A greater proportion of people with DRE resided in the most deprived regions, with 21.1% and 16.7% in the top two quintiles of the Index of Multiple Deprivation respectively, compared to < 15% in the three less deprived regions. All-cause mortality ranged from 3,687 to 4,802 per 100,000 persons with DRE, four times higher than that in the general population in the UK. Variations existed across subgroups. Considerable disease burden was observed in people with DRE in the UK. The findings emphasise the importance of early DRE diagnosis and appropriate disease management in people who develop DRE.

Risk of abnormal uterine bleeding associated with high-affinity compared with low-affinity serotonin and norepinephrine reuptake inhibitors

BackgroundConcerns have been raised about the potential association between selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs) and the risk of abnormal uterine bleeding (AUB), which may be influenced by the affinity of SSRIs/SNRIs for serotonin transporter. Thus, we assessed whether SSRIs/SNRIs with high-affinity for serotonin transporter are associated with AUB compared to SSRIs/SNRIs with low-affinity in non-pregnant women. MethodsUsing the UK Clinical Practice Research Datalink, we identified a cohort of women aged 15–24 years, newly prescribed a high- or low-affinity SSRI/SNRI between 1990 and 2019. Confounding was addressed using standardized morbidity ratio weighting. We used weighted Cox proportional hazards models to estimate the hazard ratio (HR) and 95 % confidence interval (CI) of AUB associated with high-affinity compared with low-affinity SSRIs/SNRIs. We assessed the risk of anemia as a secondary outcome. ResultsThe cohort included 156,307 users of high-affinity SSRIs/SNRIs and 102,631 users of low-affinity SSRIs/SNRIs. High-affinity SSRIs/SNRIs were not associated with an increased risk of AUB compared with low-affinity SSRIs/SNRIs (incidence rates: 46.3 versus 42.4 per 1000 person-years, respectively; HR 1.01, 95 % CI 0.93–1.09). Duration of use, age, and comorbidities did not modify the risk. However, high-affinity SSRIs/SNRIs were associated with an increased risk of anemia (HR 1.29, 95 % CI 1.04–1.61) compared with low-affinity SSRIs/SNRIs. LimitationsResidual confounding may still be present. ConclusionsThe risk of AUB did not differ between high- and low-affinity SSRIs/SNRIs. However, the potential risk of anemia suggests the need for monitoring and further investigation of the risk of AUB with these medications.

Adverse respiratory outcomes among patients with resolved asthma: matched retrospective cohort study.

Patients with asthma may have symptom remission leading to a primary care code of resolved asthma. Little is known about subsequent rates of exacerbations and respiratory tract infections (RTIs). To assess the risk of adverse respiratory outcomes for people with resolved asthma compared with those with active asthma and without asthma. This was a retrospective cohort study of patients aged >5 years, registered with a general practice in England contributing data to the Clinical Practice Research Datalink between January 2010 and December 2019. Patients with resolved asthma were matched to non-asthma controls and active asthma controls for age, sex, and practice. Negative binomial regression was used to estimate incidence rate ratios (IRRs) with 95% confidence intervals (CIs) for asthma exacerbations, RTIs, flu/pneumonia, and antibiotic prescriptions. Cohorts included 16 023 patients (8720 (54.4%) females, mean age 37 years). Compared with the active asthma cohort, the resolved cohort had fewer hospital admissions (adjusted IRR 0.29, 95% CI = 0.27 to 0.32) and general practice consultations (adjusted IRR 0.05, 95% CI = 0.04 to 0.07) for asthma exacerbations. The resolved and non-asthma cohorts had similar rates of hospital admissions for RTIs or flu/pneumonia. However, the resolved cohort had significantly greater incidence of general practice consultations for lower RTIs (adjusted IRR 2.34, 95% CI = 2.08 to 2.64) and antibiotic prescriptions (adjusted IRR 1.37, 95% CI = 1.30 to 1.44). Patients with resolved asthma had greater risk of general practice RTI and antibiotic prescription than the general population and may benefit from defined strategies for reassessing symptoms and reinitiating asthma therapy.

Eligibility of patients with chronic obstructive pulmonary disease for inclusion in randomised control trials investigating triple therapy: a study using routinely collected data

BackgroundRandomised control trials (RCTs) with strict eligibility criteria can lead to trial populations not commonly seen in clinical practice. We described the proportion of people with chronic obstructive pulmonary disease (COPD) in England eligible for RCTs investigating treatment with triple therapy.MethodsMEDLINE and Clinicaltrials.gov were searched for RCTs investigating triple therapy and eligibility criteria for each trial were extracted. Using routinely collected primary care data from Clinical Practice Research Datalink Aurum linked with Hospital Episode Statistics, we defined a population of COPD patients registered at a general practice in England, who were ≥ 40 years old, and had a history of smoking. Inclusion date was January 1, 2020. Patients who died earlier or left the general practice were excluded. Eligibility criteria for each RCT was applied to the population of COPD patients and the proportion of patients meeting each trial eligibility criteria were described.Results26 RCTs investigating triple therapy were identified from the literature. The most common eligibility criteria were post-bronchodilator FEV1% predicted 30–80%, ≥ 2 moderate/≥ 1 severe exacerbations 12-months prior, no moderate exacerbations one-month prior and no severe exacerbations three-months prior, and the use of maintenance therapy or ICS use prior to inclusion. After applying each RCT eligibility criteria to our population of 79,810 COPD patients, a median of 11.2% [interquartile range (IQR) 1.8–17.4] of patients met eligibility criteria. The most discriminatory criteria included the presence exacerbations of COPD and previous COPD related medication use with a median of 67.6% (IQR 8.5–73.4) and 63% (IQR 69.3–38.4) of COPD patients not meeting these criteria, respectively.ConclusionData from these RCTs may not be generalisable to the wider population of people with COPD seen in everyday clinical practice and real-world evidence studies are needed to supplement trials to understand effectiveness in all people with COPD.

The effectiveness of COVID-19 vaccines to prevent long COVID symptoms: staggered cohort study of data from the UK, Spain, and Estonia

Although vaccines have proved effective to prevent severe COVID-19, their effect on preventing long-term symptoms is not yet fully understood. We aimed to evaluate the overall effect of vaccination to prevent long COVID symptoms and assess comparative effectiveness of the most used vaccines (ChAdOx1 and BNT162b2). We conducted a staggered cohort study using primary care records from the UK (Clinical Practice Research Datalink [CPRD] GOLD and AURUM), Catalonia, Spain (Information System for Research in Primary Care [SIDIAP]), and national health insurance claims from Estonia (CORIVA database). All adults who were registered for at least 180 days as of Jan 4, 2021 (the UK), Feb 20, 2021 (Spain), and Jan 28, 2021 (Estonia) comprised the source population. Vaccination status was used as a time-varying exposure, staggered by vaccine rollout period. Vaccinated people were further classified by vaccine brand according to their first dose received. The primary outcome definition of long COVID was defined as having at least one of 25 WHO-listed symptoms between 90 and 365 days after the date of a PCR-positive test or clinical diagnosis of COVID-19, with no history of that symptom 180 days before SARS-Cov-2 infection. Propensity score overlap weighting was applied separately for each cohort to minimise confounding. Sub-distribution hazard ratios (sHRs) were calculated to estimate vaccine effectiveness against long COVID, and empirically calibrated using negative control outcomes. Random effects meta-analyses across staggered cohorts were conducted to pool overall effect estimates. A total of 1 618 395 (CPRD GOLD), 5 729 800 (CPRD AURUM), 2 744 821 (SIDIAP), and 77 603 (CORIVA) vaccinated people and 1 640 371 (CPRD GOLD), 5 860 564 (CPRD AURUM), 2 588 518 (SIDIAP), and 302 267 (CORIVA) unvaccinated people were included. Compared with unvaccinated people, overall HRs for long COVID symptoms in people vaccinated with a first dose of any COVID-19 vaccine were 0·54 (95% CI 0·44-0·67) in CPRD GOLD, 0·48 (0·34-0·68) in CPRD AURUM, 0·71 (0·55-0·91) in SIDIAP, and 0·59 (0·40-0·87) in CORIVA. A slightly stronger preventative effect was seen for the first dose of BNT162b2 than for ChAdOx1 (sHR 0·85 [0·60-1·20] in CPRD GOLD and 0·84 [0·74-0·94] in CPRD AURUM). Vaccination against COVID-19 consistently reduced the risk of long COVID symptoms, which highlights the importance of vaccination to prevent persistent COVID-19 symptoms, particularly in adults. National Institute for Health and Care Research.

Prevalence, incidence and healthcare burden of eosinophilic granulomatosis with polyangiitis in the UK.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare but serious disease characterised by the combination of small-to-medium vessel vasculitis, blood and tissue eosinophilia, and asthma and/or sinonasal disease. This study estimated the prevalence and incidence of diagnosed EGPA in the United Kingdom (UK), and described the demographics, clinical characteristics and healthcare resource utilisation (HCRU) of this population. This retrospective longitudinal study of patients with newly diagnosed EGPA (index) (2005-2019) used the Clinical Practice Research Datalink AURUM and Hospital Episode Statistics databases. The primary outcomes were the annual prevalence (2005-2019) and incidence (2006-2019) of EGPA, and secondary outcomes included patient demographics and clinical characteristics, and HCRU in the year pre- and post-index (diagnosis). Populations of patients with EGPA comprised 940 prevalent cases and 502 incident cases, of which 377 were linked to Hospital Episode Statistics. EGPA prevalence increased from 22.7 to 45.6 cases per 1 000 000 (2005-2019), driven by patients aged ≥18 years. Incidence ranged from 2.3 to 4.0 per 1 000 000 person-years (2006-2019). Pre-index, the most common clinical symptoms were respiratory related, and the most common comorbidities were asthma (80.6%) and nasal polyps (32.1%). Post-index, 19.1% had an EGPA-related inpatient stay (median length of stay 11.0 days) and 38.7% had five or more oral corticosteroid (OCS) prescriptions with a mean OCS possession ratio per patient of 47.0%. Although EGPA incidence in the UK remains relatively stable, prevalence is increasing, and HCRU and OCS use remain frequent, suggesting considerable healthcare burden for patients with EGPA.

Clostridioides difficile infections, recurrences, and clinical outcomes in real-world settings from 2015 to 2019: The RECUR England study

ObjectiveTo estimate the epidemiological and clinical burden of Clostridioides difficile infections (CDIs) and recurrences (rCDIs) in England. MethodsThis retrospective study included adult patients diagnosed with CDI (community or hospital settings) over 2015-2019 from Clinical Practice Research Datalink and Hospital Episode Statistics databases. Incidences of CDI and rCDI were determined annually. Time to subsequent rCDI was estimated by Kaplan-Meier method. Rates of complications were assessed within 12 months from index episode. Association of risk factors with complications was evaluated using a Cox regression model. ResultsA total of 52,443 CDI episodes were recorded among 36,913 patients. Of these, 75% were aged ≥65 years, 59% were women; 73% were treated in community settings. CDI incidence remained stable (111 episodes per 100,000 patients in 2019). Around 21% of patients had ≥1 rCDI. Sepsis (12%) was the most common complication, followed by colectomy and ulcerative colitis. Age, gender, comorbidities, rCDI, preindex medical procedures, hospitalizations and consultations, and CDI treatment in hospital, were found to increase the risk of complication. ConclusionsCDI remains a concern in England. The study highlights the importance of managing primary and rCDI episodes via effective and improved therapies to prevent fatal complications.

Persons diagnosed with COVID-19 in England in the Clinical Practice Research Datalink (CPRD): a cohort description

ObjectiveTo create case definitions for confirmed COVID-19 diagnoses, COVID-19 vaccination status and three separate definitions of high risk of severe COVID-19, as well as to assess whether the implementation of...

Healthcare resource utilisation and associated costs of adult attention deficit hyperactivity disorder in England

Background Attention deficit hyperactivity disorder is generally widely under-recognised and undertreated in adults. Real world evidence is needed to characterise healthcare resource utilisation and economic burden of adult attention deficit hyperactivity disorder in England. Methods This retrospective cohort study used primary care medical records (Clinical Practice Research Datalink – Aurum) linked to secondary care data (hospital episode statistics). Patients were indexed on their first-ever record of an attention deficit hyperactivity disorder diagnosis, made during adulthood, between 1 January 2016 and 30 June 2018. Healthcare resource utilisation and associated costs were compared 18-months before and after diagnosis. Results 2236 patients were included; mood disorders and anxiety were recorded in 47.1% and 46.2%, respectively. In 2153 patients with available data for both periods, mean total healthcare resource utilisation cost per patient was £408.6 (95% CI £264.4–£552.8) higher in the post- versus pre-index period (p &lt; 0.001). The mean prescriptions cost per patient doubled (£322.5 versus £614.5) and represented the largest proportional cost increase post-diagnosis compared to other healthcare resource utilisation costs measured. Discussion An attention deficit hyperactivity disorder diagnosis in adulthood ensures patients receive appropriate treatment for attention deficit hyperactivity disorder and comorbid anxiety and depression. Total healthcare resource utilisation costs appeared to increase post attention deficit hyperactivity disorder diagnosis; however, further studies are required to confirm this. This cost increase should be set in the context of multiple societal benefits likely to accrue from the effective management of adult attention deficit hyperactivity disorder.

Predicting incident heart failure from population-based nationwide electronic health records: protocol for a model development and validation study

IntroductionHeart failure (HF) is increasingly common and associated with excess morbidity, mortality, and healthcare costs. Treatment of HF can alter the disease trajectory and reduce clinical events in HF. However,...

Sexual and reproductive health and rights of migrant women attending primary care in England: A population-based cohort study of 1.2 million individuals of reproductive age (2009–2018)

BackgroundEvidence on the sexual and reproductive health and rights (SRHR) of migrants is lacking globally. We describe SRHR healthcare resource use and long-acting reversible contraceptives (LARCs) prescriptions for migrant versus non-migrant women attending primary care in England (2009–2018). MethodsThis population-based observational cohort study, using Clinical Practice Research Datalink (CPRD) GOLD, included females living in England aged 15 to 49. Migration was defined using a validated codelist. Rates per 100 person years at risk (pyar) and adjusted rate ratios (RRs) were measured in migrants versus non-migrants for consultations related to all-causes, six exemplar SRHR outcomes, and LARC prescriptions. Proportions of migrants and non-migrants ever prescribed LARC were calculated. FindingsThere were 25,112,116 consultations across 1,246,353 eligible individuals. 98,214 (7.9 %) individuals were migrants. All-cause consultation rates were lower in migrants versus non-migrants (509 vs 583/100pyar;RR 0.9;95 %CI 0.9–0.9), as were consultations rates for emergency contraception (RR 0.7;95 %CI 0.7–0.7) and cervical screening (RR 0.96;95 %CI 0.95–0.97). Higher rates of consultations were found in migrants for abortion (RR 1.2;95 %CI 1.1–1.2) and management of fertility problems (RR 1.39;95 %CI 1.08–1.79). No significant difference was observed for chlamydia testing and domestic violence. Of 1,205,258 individuals eligible for contraception, the proportion of non-migrants ever prescribed LARC (12.2 %;135,047/1,107,894) was almost double that of migrants (6.91 %;6,728/97,364). Higher copper intrauterine devices prescription rates were found in migrants (RR 1.53;95 %CI 1.45–1.61), whilst hormonal LARC rates were lower for migrants: levonorgestrel intrauterine device (RR 0.63;95 %CI 0.60–0.66), subdermal implant (RR 0.72;95 %CI 0.69–0.75), and progesterone-only injection (RR 0.35;95 %CI 0.34–0.36). InterpretationHealthcare resource use differs between migrant and non-migrant women of reproductive age. Opportunities identified for tailored interventions include access to primary care, LARCs, emergency contraception and cervical screening. An inclusive approach to examining health needs is essential to actualise sexual and reproductive health as a human right.

Incident dementia risk among patients with type 2 diabetes receiving metformin versus alternative oral glucose-lowering therapy: an observational cohort study using UK primary healthcare records

Introduction4.2 million individuals in the UK have type 2 diabetes, a known risk factor for dementia and mild cognitive impairment (MCI). Diabetes treatment may modify this association, but existing evidence...

Initiation patterns of anticoagulants for atrial fibrillation among older UK adults with and without chronic kidney disease, 2010–2020

BackgroundThere is a paucity of data on the initiation patterns of anticoagulants among older atrial fibrillation patients with and without chronic kidney disease (CKD).Setting and methodsWe used the UK Clinical...